The long-range objective of the proposed research is to identify and analyze in sequential fashion, the key cellular and molecular events occurring and during oral carcinogenesis. Viable cell dissociates, full thickness whole mounts, and cryostatprepared microscope sections, of carcinogen-treated hamster buccal pouch epithelium (HBPE) will be examined for functional, histochemical, immunohistochemical, and morphological evidence of cells which have undergone one or more steps in the carcinogenic Process. The specific aims are: 1) to (a) further characterize a unique keratinocyte population identified in cultures of carcinogen- initiated HBPE, and (b) evaluate its neoplastic potential using assays for production of transforming growth factors, in vitro growth characteristics, angiogenesis, and tumor formation following reimplantation into the autologous host, 2) to detect presumptive precancerous lesions in carcinogen-initiated HBPE using monoclonal antibodies against specific oncogene products, and 3) to determine whether extractable constituents of smokeless tobacco exert a promoting action on HBPE with an accompanying selection of focal cell populations rich in gamma-glutamyl transpeptidase activity. This research is based on the premise that a detailed analysis of oral carcinogenesis, which focuses on the relevant participating cell populations, will contribute to improved strategies for early detection of precancerous oral lesions and prevention of oral cancer.